Learn and Understand: The definition of cell changes again The - - PowerPoint PPT Presentation

Learn and Understand:

• The definition of “cell” changes again
• The contractile unit of muscle is the sarcomere.
• ATP and Ca2+ must be available for muscle to contract

and relax.

• Skeletal muscle is stimulated to contract by neurons of

the CNS. Nervous system controls force applied.

• Ion movement and changes in electrical potential across

the sarcolemma is the ultimate signal for contraction.

• Muscle cells vary in their ability to use sources of energy

and their speed of contraction. Muscular System with Special Emphasis on Skeletal Muscle Anatomy and Physiology

Muscle Functions

• Four important functions

– Movement of bones or fluids (e.g., blood) – Maintaining posture and body position – Stabilizing joints – Heat generation (especially skeletal muscle)

• Additional functions

– Protects organs, forms valves, controls pupil size, causes "goosebumps" Special Characteristics of Muscle Tissue

• Excitability (responsiveness): ability to receive and respond to

stimuli

• Contractility: ability to shorten forcibly when stimulated
• Elasticity: ability to stretch beyond resting length and recoil

Muscle Tissue

• Nearly half of body's mass

– Female skeletal muscle makes up 36% of body mass – Male skeletal muscle makes up 42% of body mass, primarily due to testosterone

• Transforms chemical energy (ATP) to directed

mechanical energy → exerts force

• Three types

– Skeletal – Cardiac – Smooth

• Myo, mys, and sarco - prefixes for muscle

Figure 9.1 Connective tissue sheaths of skeletal muscle: epimysium, perimysium, and endomysium.

Bone Tendon Epimysium Epimysium Perimysium Endomysium Muscle fiber in middle of a fascicle Blood vessel Perimysium wrapping a fascicle Endomysium (between individual muscle fibers) Muscle fiber Perimysium Fascicle

Skeletal Muscles

• Each muscle served by one artery, one nerve,

and one or more veins

• Connective tissue sheaths of skeletal muscle

– External to internal

• Epimysium: dense irregular connective tissue
• Perimysium: fibrous connective tissue surrounding

fascicles

• Endomysium: fine areolar connective tissue

Skeletal Muscle Fibers: Anatomy

• Long, cylindrical cell up to 30 cm long
• Multiple nuclei
• Sarcolemma
• Sarcoplasm

– Glycosomes for glycogen storage, myoglobin for O2 storage – amount of each dependent on muscle type

• Modified structures: myofibrils, sarcoplasmic

reticulum, and T tubules

Figure 9.2b Microscopic anatomy of a skeletal muscle fiber. Sarcolemma Mitochondrion Myofibril Nucleus Light I band Dark A band

Thin (actin) filament Z disc H zone Z disc Thick (myosin) filament I band A band I band M line Sarcomere

Figure 9.2d Microscopic anatomy of the sarcomere

Z disc Sarcomere M line Z disc Thin (actin) filament Elastic (titin) filaments Thick (myosin) filament

Longitudinal section of filaments within one sarcomere of a myofibril

Thick filament Thin filament In the center of the sarcomere, the thick filaments lack myosin heads. Myosin heads are present only in areas of myosin-actin overlap.

Thick filament. Thin filament

Each thick filament consists of many myosin molecules whose heads protrude at oppositeends

• f the filament.

A thin filament consists of two strands of actin subunits twisted into a helix plus two types of regulatory proteins (troponin and tropomyosin).

Portion of a thick filament Portion of a thin filament Myosin head Tropomyosin Troponin Actin Actin-binding sites ATP- binding site Heads Tail Flexible hinge region Myosin molecule Actin subunits Actin subunits Active sites for myosin attachment

Figure 9.5 Relationship of the sarcoplasmic reticulum and T tubules to myofibrils and sarcomeres of skeletal muscle.

Part of a skeletal muscle fiber (cell) Myofibril Sarcolemma I band A band I band Z disc H zone Z disc M line Sarcolemma Triad:

• T tubule
• Terminal

cisterns of the SR (2) Tubules of the SR Myofibrils Mitochondria

Triad Relationships

• T tubules conduct impulses deep into muscle fiber;

every sarcomere

• Integral proteins protrude into intermembrane space

from T tubule and SR cistern membranes and connect with each other

• T tubule integral proteins act as voltage sensors and

change shape in response to voltage changes

• SR integral proteins are channels that release Ca2+

from SR cisterns when voltage sensors change shape

Sliding Filament Model of Muscle Contraction

• In relaxed state, thin and thick filaments
• verlap only at ends of A band
• Actin myofilaments are pulled (slide) over

myosin to shorten sarcomeres – Actin and myosin do not change length – Occurs when myosin heads bind to actin

• Shortening occurs when tension generated by

cross bridges on thin filaments exceeds forces

• pposing shortening

Figure 9.6 Sliding filament model of contraction. Slide 2

1 Fully relaxed sarcomere of a muscle fiber Z H Z I I A

Figure 9.6 Sliding filament model of contraction. Slide 3

2 Fully contracted sarcomere of a muscle fiber Z Z I I A

Figure 9.22 Length-tension relationships of sarcomeres in skeletal muscles.

Sarcomeres greatly shortened Sarcomeres at resting length Sarcomeres excessively stretched Optimal sarcomere

• perating length

(80%–120% of resting length) Tension (percent of maximum) 100 50 60 80 100 120 140 160 180 Percent of resting sarcomere length 75% 100% 170%

Stimulus for Contraction: Upsetting Ion Concentrations at the Sarcolemma

• Resting membrane potential (RMP) maintained

by active transport

– Just outside the sarcolemma: high Na+ concentration, some Cl-, some K+ – Just inside the sarcolemma: high K+ and negatively- charged proteins

• Action potential (AP) stimulates contraction
• changes to membrane permeability resulting in ion movement
• Voltage change is the stimulus
• Resting potential re-established almost

immediately

Polarized Membrane: Resting Membrane Potential

• 90 mV

potential across membrane

Explanation of Resting Membrane Potential at Sarcolemma

Plasma membrane Unequally-distributed ions Membrane is POLARIZED

Ion Channel Role in Maintaining/Upsetting Potential

• Types

– Ligand-gated. Ligands are molecules that bind to receptors.

• Receptor: protein or glycoprotein with a receptor

site

• Example ligand: neurotransmitters

– Voltage-gated

• Open and close in response to small voltage

changes across plasma membrane

• Each is specific for one ion

Resting Potential

What’s missing:

• Open K+ channels
• Na+/K+ pump

Activation Gate Inactivation gate

Action Potentials

• Phases

– Graded (end plate) potential at NMJ – Threshold – Depolarization – Repolarization

• All-or-none principle
• Propagation

RMP

• 50 to -55

mV

Action Potential

Resting Depolarization Repolarization

Figure 9.10 Action potential tracing indicates changes in Na+ and K+ ion channels.

Membrane potential (mV) +30

–95 5 10 15 20

Depolarization due to Na+ entry Na+ channels close, K+ channels

• pen

Repolarization due to K+ exit K+ channels closed Na+ channels

• pen

Time (ms)

The Nerve Stimulus and Events at the Neuromuscular Junction

• Skeletal muscles stimulated by somatic motor

neurons

• Axons of motor neurons travel from central

nervous system via nerves to skeletal muscle

• Each axon forms several branches as it enters

muscle

• Each axon ending forms neuromuscular

junction with single muscle fiber

– Usually only one per muscle fiber – Situated midway along length of muscle fiber

Figure 9.8 When a nerve impulse reaches a neuromuscular junction, acetylcholine (ACh) is released.

Action potential (AP) Myelinated axon

• f motor neuron

Axon terminal of neuromuscular junction Sarcolemma of the muscle fiber Synaptic vesicle containing ACh Synaptic cleft Junctional folds of sarcolemma Sarcoplasm of muscle fiber Postsynaptic membrane ion channel opens; ions pass. Ion channel closes; ions cannot pass. Axon terminal

• f motor neuron

Fusing synaptic vesicles Degraded ACh ACh Acetylcho- linesterase ACh

Figure 9.9 Summary of events in the generation and propagation of an action potential in a skeletal muscle fiber.

Open Na+ channel Na+ Closed K+ channel K+ Action potential Axon terminal of neuromuscular junction ACh-containing synaptic vesicle Ca2+ Ca2+ Synaptic cleft Wave of depolarization Closed Na+ channel Open K+ channel Na+ K+

– – – – – – – – – – – – – – – – – – – + + + + – – – – + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + – – – – – – – – – – – – – – – – – – – – – –

1. Nerve impulse arrives at axon terminal acetylcholine released by synaptic terminal into synaptic cleft 2. ACh diffuses across cleft and binds with nicotinic (excitatory) receptors on sarcolemma opening sodium ion gates 3. Sodium influx depolarizes sarcolemma to threshold 4. Propagation of AP away from NMJ along fiber sarcolemma

Action Potential Propagation

Propagation in

• ne direction only

due to refractory period

Synaptic cleft Axon terminal of motor neuron at NMJ Action potential is generated ACh Muscle fiber T tubule Terminal cistern

• f SR

Triad One sarcomere One myofibril Sarcolemma Steps in E-C Coupling: Terminal cistern

• f SR

Ca2+ release channel Voltage-sensitive tubule protein T tubule Sarcolemma 1 2 3 4 Myosin cross bridge Active sites exposed and ready for myosin binding Myosin Tropomyosin blocking active sites Actin Troponin

Excitation-Contraction (E-C) Coupling

• Events that transmit AP along sarcolemma lead to sliding of

myofilaments

• AP brief; ends before contraction

– Causes rise in intracellular Ca2+ which initiates contraction

Role of Calcium (Ca2+) in Contraction

• At low intracellular Ca2+ concentration

– Tropomyosin blocks active sites – Myosin heads cannot attach to actin – Muscle fiber relaxed

• At higher intracellular Ca2+ concentrations

– Ca2+ binds to troponin

• Troponin changes shape and moves tropomyosin away

from myosin-binding sites

• Myosin heads bind to actin

– When nervous stimulation ceases, Ca2+ pumped back into SR and contraction ends

Figure 9.12 The cross bridge cycle is the series of events during which myosin heads pull thin filaments toward the center of the sarcomere.

A&P Flix™: The Cross Bridge Cycle

PLAY

Actin Ca2+ Thin filament Myosin cross bridge Thick filament Myosin ATP hydrolysis In the absence

• f ATP, myosin

heads will not detach, causing RIGOR MORTIS.

*This cycle will continue as long as ATP is available and Ca2+ is bound to troponin.

1 2 3 4

Relaxation

• Ca2+ moves away from troponin-tropomyosin

complex causing ‘relaxation’

• Ca2+ diffuses out of the myofibril

– Transported back into sarcoplasmic reticulum by active transport.

• Troponin-tropomyosin complex re-establishes its

position and blocks binding sites.

– Myosin cannot form cross bridges, filaments cannot slide

• Muscle recoil

– Sarcomere elements, connective tissue, antagonistic muscle action and opposing forces, gravity

Phase 1 Motor neuron stimulates muscle fiber (see Figure 9.8). Phase 2: Excitation-contraction coupling occurs (see Figures 9.9 and 9.11). Action potential (AP) arrives at axon terminal at neuromuscular junction ACh released; binds to receptors

• n sarcolemma

Ion permeability of sarcolemma changes Local change in membrane voltage (depolarization) occurs Local depolarization (end plate potential) ignites AP in sarcolemma AP travels across the entire sarcolemma AP travels along T tubules SR releases Ca2+; Ca2+ binds to troponin; myosin-binding sites (active sites) on actin exposed Myosin heads bind to actin; contraction begins

Figure 9.7 The phases leading to muscle fiber contraction.

Principles of Muscle Mechanics

• Same principles apply to contraction of single

fiber and whole muscle

• Contraction produces muscle tension, force

exerted on load or object to be moved

Figure 9.14a The muscle fiber twitch.

Latent period Period of contraction Period of relaxation Percentage of maximum tension Single stimulus Time (ms) 140 120 100 80 60 40 20

Myogram showing the three phases of an isometric twitch

Latent period Time when E-C coupling events occur Time between AP initiation and beginning of contraction

Motor Unit: The Nerve-Muscle Functional Unit

• Each muscle served by at least one motor

nerve

– Motor nerve contains axons of up to hundreds of motor neurons – Axons branch into terminals, each of which → NMJ with single muscle fiber

• Motor unit = motor neuron and all (four to

several hundred) muscle fibers it supplies

– Smaller number = fine control

Figure 9.13 A motor unit consists of one motor neuron and all the muscle fibers it innervates.

Spinal cord Motor unit 1 Motor unit 2 Axon terminals at neuromuscular junctions Branching axon to motor unit Motor neuron cell body Motor neuron axon Muscle Muscle fibers Nerve Branching axon terminals form neuromuscular junctions, one per muscle fiber (photomicro- graph 330x). Axons of motor neurons extend from the spinal cord to the muscle. There each axon divides into a number of axon terminals that form neuromuscular junctions with muscle fibers scattered throughout the muscle.

Motor Unit

• Muscle fibers from motor unit spread

throughout muscle so single motor unit causes weak contraction of entire muscle

• Motor units in muscle usually contract

asynchronously; helps prevent fatigue

Graded Muscle Responses

• Graded muscle responses

– Varying strength of contraction for different demands

• Required for proper control of skeletal

movement

• Responses graded by
• 1. Changing frequency of stimulation
• 2. Changing strength of stimulation

Figure 9.15a A muscle's response to changes in stimulation frequency.

Single stimulus single twitch Contraction Maximal tension of a single twitch Relaxation Stimulus 300 200 100 Time (ms) Tension

Figure 9.15b A muscle's response to changes in stimulation frequency.

Low stimulation frequency unfused (incomplete) tetanus Partial relaxation Time (ms) If another stimulus is applied before the muscle relaxes completely, then more tension results. This is wave (or temporal) summation and results in unfused (or incomplete) tetanus. Tension 300 200 100 Stimuli

Figure 9.15c A muscle's response to changes in stimulation frequency.

High stimulation frequency fused (complete) tetanus Stimuli At higher stimulus frequencies, there is no relaxation at all between stimuli. This is fused (complete) tetanus. Tension Time (ms) 300 200 100

Response to Change in Stimulus Strength

• Recruitment (multiple motor unit summation)

controls force of contraction

– Subthreshold stimuli – no observable contractions – Threshold stimulus: stimulus strength causing first

• bservable muscle contraction

– Maximal stimulus – strongest stimulus that increases contractile force

Figure 9.16 Relationship between stimulus intensity (graph at top) and muscle tension (tracing below). Stimulus strength Stimulus voltage Threshold stimulus Maximal stimulus 10 9 8 7 6 5 4 3 2 1 Proportion of motor units excited Strength of muscle contraction Maximal contraction Time (ms) Tension Stimuli to nerve

Frog Gastrocnemius

Muscle Tone

• Constant, slightly contracted state of all

muscles

• Due to spinal reflexes

– Groups of motor units alternately activated in response to input from stretch receptors in muscles

• Keeps muscles firm, healthy, and ready to

respond

• Less active when lying down or asleep

Muscle Metabolism: Energy for Contraction

• ATP only source used directly to move and

detach cross bridges, calcium pumps in SR, return of Na+ & K+ after excitation-contraction coupling

• Available stores of ATP depleted in 4–6

seconds

• ATP regenerated by:

– Direct phosphorylation of ADP by creatine phosphate (CP) – Anaerobic pathway (glycolysis → lactic acid) – Aerobic respiration

Direct phosphorylation

Coupled reaction of creatine Phosphate (CP) and ADP Energy source: CP Oxygen use: None Products: 1 ATP per CP, creatine Duration of energy provided: 15 seconds Creatine kinase Creatine

Anaerobic pathway

Glycolysis and lactic acid formation Energy source: glucose Glucose (from glycogen breakdown or delivered from blood) Glycolysis in cytosol Pyruvic acid net gain Released to blood Lactic acid Oxygen use: None Products: 2 ATP per glucose, lactic acid Duration of energy provided: 30-40 seconds, or slightly more 2

Anaerobic Pathway

• Glycolysis – does not require oxygen
• At 70% of maximum contractile activity

– Bulging muscles compress blood vessels; oxygen delivery impaired

• Anaerobic respiration yields only 5% as much

ATP as aerobic respiration, but produces ATP 2½ times faster

• Anaerobic threshold

– Point at which muscle metabolism converts to anaerobic

Aerobic pathway

Aerobic cellular respiration Energy source: glucose; pyruvic acid; free fatty acids from adipose tissue; amino acids from protein catabolism Glucose (from glycogen breakdown or delivered from blood) Pyruvic acid Fatty acids Amino acids net gain per glucose Oxygen use: Required Products: 32 ATP per glucose, CO2, H2O Duration of energy provided: Hours Aerobic respiration in mitochondria Aerobic respiration in mitochondria

32

• Produces 95% of ATP during rest

and light to moderate exercise; slow

• Series of chemical reactions that

require oxygen

• Fuels:
• 1. stored glycogen
• 2. then bloodborne glucose
• 3. pyruvic acid from glycolysis
• 4. and free fatty acids
• Aerobic endurance
• Length of time muscle

contracts using aerobic pathways

Figure 9.20 Comparison of energy sources used during short-duration exercise and prolonged-duration exercise.

Short-duration exercise 6 seconds ATP stored in muscles is used first. 10 seconds ATP is formed from creatine phosphate and ADP (direct phosphorylation). 30–40 seconds Glycogen stored in muscles is broken down to glucose, which is oxidized to generate ATP (anaerobic pathway). End of exercise Prolonged-duration exercise Hours ATP is generated by breakdown

• f several nutrient energy fuels by

aerobic pathway.

Muscle Fatigue

• Physiological inability to contract despite

continued stimulation

• Occurs when

– Ionic imbalances (K+, Ca2+, Pi) interfere with E-C coupling – Prolonged exercise may damage SR and interferes with Ca2+ regulation and release

• Total lack of ATP occurs rarely, during states of

continuous contraction, and causes contractures (continuous contractions)

– Includes rigor mortis

Excess Postexercise Oxygen Consumption

• To return muscle to resting state

– Oxygen reserves replenished – Lactic acid converted to pyruvic acid – Glycogen stores replaced – ATP and creatine phosphate reserves replenished

• All require extra oxygen; occurs post exercise

Muscle Fiber Type

• Most muscles contain mixture of fiber types
• Classified according to two characteristics

– Speed of contraction: slow or fast fibers according to

• Speed at which myosin ATPases split ATP
• Pattern of electrical activity of motor neurons

– Metabolic pathways for ATP synthesis

• Oxidative fibers—use aerobic pathways

– Slow oxidative fibers; Fast oxidative fibers;

• Glycolytic fibers—use anaerobic glycolysis

– Fast glycolytic fibers

• All fibers in one motor unit same type

– Genetics dictate individual's percentage of each – Training can aid in development of what you currently have